Increased SOX2 expression in salivary gland carcinoma ex pleomorphic adenoma progression: an association with adverse outcome.

SOX2 is a regulatory factor of embryonic stem cells that has been implicated in carcinogenesis and cancer progression. We aimed to investigate the potential role of SOX2 in the stepwise progression from pleomorphic adenoma (PA) to invasive carcinoma ex pleomorphic adenoma (CXPA), evaluating its prognostic significance as well. Thirty PAs without malignant transformation and 25 CXPAs presenting both luminal or myoepithelial differentiation (7 intracapsular and 18 extracapsular) were evaluated immunohistochemically for SOX2 expression. Of these, 24 CXPAs (96%) were positive to SOX2, being 6 intracapsular carcinomas (85.7%) and all the 18 extracapsular carcinomas (100%). Residual PA areas and PA without malignant transformation were negative. High SOX2 expression levels (> 50% of positive cells) were correlated with high histological grade (p = 0.02), brisk mitotic activity (p = 0.01), advanced pT stage (p = 0.01), tumor recurrence (p = 0.01), and development of distant metastasis (p = 0.004). Still, overall survival rates were shorter in patients with extracapsular CXPA exhibiting diffuse SOX2 expression. These results suggest that SOX2 may play an important role in carcinogenesis and progression of CXPA and is also related with prognostic indicators in CXPAs with extracapsular invasion. Although direct therapeutic intervention in SOX2 may result in unwanted complications due to its constitutive functions, strategic approach to SOX2-related pathways may provide new therapeutic opportunities for patients with invasive CXPA.